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http://hdl.handle.net/2445/116575
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DC Field | Value | Language |
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dc.contributor.author | Pourcet, Benoit | - |
dc.contributor.author | Gage, Matthew C. | - |
dc.contributor.author | León Moreno, Theresa Elizabeth | - |
dc.contributor.author | Waddington, Kirsty E. | - |
dc.contributor.author | Pello, Oscar M. | - |
dc.contributor.author | Steffensen, Knut R. | - |
dc.contributor.author | Castrillo, Antonio | - |
dc.contributor.author | Valledor Fernández, Annabel | - |
dc.contributor.author | Pineda-Torra, Inés | - |
dc.date.accessioned | 2017-10-13T12:10:06Z | - |
dc.date.available | 2017-10-13T12:10:06Z | - |
dc.date.issued | 2016-05-06 | - |
dc.identifier.issn | 2045-2322 | - |
dc.identifier.uri | http://hdl.handle.net/2445/116575 | - |
dc.description.abstract | IL-18 is a member of the IL-1 family involved in innate immunity and inflammation. Deregulated levels of IL-18 are involved in the pathogenesis of multiple disorders including inflammatory and metabolic diseases, yet relatively little is known regarding its regulation. Liver X receptors or LXRs are key modulators of macrophage cholesterol homeostasis and immune responses. Here we show that LXR ligands negatively regulate LPS-induced mRNA and protein expression of IL-18 in bone marrow-derived macrophages. Consistent with this being an LXR-mediated process, inhibition is abolished in the presence of a specific LXR antagonist and in LXR-deficient macrophages. Additionally, IL-18 processing of its precursor inactive form to its bioactive state is inhibited by LXR through negative regulation of both pro-caspase 1 expression and activation. Finally, LXR ligands further modulate IL-18 levels by inducing the expression of IL-18BP, a potent endogenous inhibitor of IL-18. This regulation occurs via the transcription factor IRF8, thus identifying IL-18BP as a novel LXR and IRF8 target gene. In conclusion, LXR activation inhibits IL-18 production through regulation of its transcription and maturation into an active pro-inflammatory cytokine. This novel regulation of IL-18 by LXR could be applied to modulate the severity of IL-18 driven metabolic and inflammatory disorders. | - |
dc.format.extent | 12 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Nature Publishing Group | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1038/srep25481 | - |
dc.relation.ispartof | Scientific Reports, 2016, vol. 6, p. 25481 | - |
dc.relation.uri | https://doi.org/10.1038/srep25481 | - |
dc.rights | cc-by (c) Pourcet et al., 2016 | - |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es | - |
dc.source | Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia) | - |
dc.subject.classification | Receptors nuclears (Bioquímica) | - |
dc.subject.classification | Macròfags | - |
dc.subject.other | Nuclear receptors (Biochemistry) | - |
dc.subject.other | Macrophages | - |
dc.title | The nuclear receptor lxr modulates interleukin-18 levels in macrophages through multiple mechanisms | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 662351 | - |
dc.date.updated | 2017-10-13T12:10:06Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 27149934 | - |
Appears in Collections: | Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia) |
Files in This Item:
File | Description | Size | Format | |
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662351.pdf | 1.15 MB | Adobe PDF | View/Open |
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